General reproduction, perinatal-postnatal, and teratology studies of nitrofurantoin macrocrystals in rats and rabbits.

Urinary tract infections in pregnant women are common and require prompt, effective treatment. Currently, no antibacterial agents have received regulatory approbation for use without restriction during pregnancy. The choice of a drug for use in pregnant women requires careful examination of its possible maternal and fetal toxicity as well as its teratogenic potential. We conducted studies to determine the effects of nitrofurantoin macrocrystals (Macrodantin, Norwich Eaton Pharmaceuticals, Inc.), a synthetic antibacterial, on reproductive capability, fetal development, and neonatal survival in the rat and the rabbit. Doses of 10.0, 20.0, and 30.0 mg/kg.d, approximately 2, 4, and 6 times the daily human therapeutic dose, were administered orally in a methylcellulose suspension to rats and rabbits in general reproduction, perinatal-postnatal, and teratology studies. Safety was assessed by evaluating reproductive capability, fertility, gestation period, fetal and neonatal death, litter size and viability, birth weight and postnatal growth, and malformations. Under the conditions of these studies, treatment with nitrofurantoin macrocrystals in rats and rabbits before or during pregnancy or during lactation caused no adverse effects in the mother, fetus, or neonate. These findings support the premise that nitrofurantoin macrocrystals constitute a safe treatment for urinary tract infection during pregnancy.